Dominant Leber congenital amaurosis, cone-rod degeneration, and retinitis pigmentosa caused by mutant versions of the transcription factor CRX

Détails

ID Serval
serval:BIB_DD181B653BB0
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Institution
Titre
Dominant Leber congenital amaurosis, cone-rod degeneration, and retinitis pigmentosa caused by mutant versions of the transcription factor CRX
Périodique
Human Mutation
Auteur(s)
Rivolta  C., Berson  E. L., Dryja  T. P.
ISSN
1098-1004 (Electronic)
Statut éditorial
Publié
Date de publication
12/2001
Peer-reviewed
Oui
Volume
18
Numéro
6
Pages
488-98
Notes
Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Review --- Old month value: Dec
Résumé
We summarize 18 mutations in the human CRX gene that have been associated with Leber congenital amaurosis (congenital retinal blindness), cone-rod degeneration, or retinitis pigmentosa. Except for one obviously null allele not definitely associated with a phenotype (a frameshift in codon 9), all CRX mutations appear to be completely penetrant and cause disease in heterozygotes. These dominant alleles fall into two categories. In one group are missense mutations and short, in-frame deletions; in the second group are frameshift mutations, all of which are in the last exon. All of these dominant mutations are likely to produce stable mRNA that is translated. Mutations in the missense group preferentially affect the conserved homeobox (codons 39-98), and all frameshift mutations leave the homeodomain intact but alter the OTX motif encoded by codons 284-295 at the carboxy terminus. We could not uncover any correlation between type of disease (congenital amaurosis vs. cone-rod degeneration or retinitis pigmentosa) and the type of mutation (missense vs. frameshift). Four of the 18 mutations (approximately 20%) were de novo mutations, and all of these were found in isolate cases of Leber congenital amaurosis. Dominant CRX mutations have not been associated with mental retardation or developmental delay that has sometimes been found in Leber congenital amaurosis caused by other genes. Implications regarding potential future therapies are discussed.
Mots-clé
Genes, Dominant/genetics Homeodomain Proteins/*genetics Humans Mutation Optic Atrophy, Hereditary, Leber/*genetics Retinitis Pigmentosa/*genetics Trans-Activators/*genetics
Pubmed
Web of science
Création de la notice
24/01/2008 14:14
Dernière modification de la notice
20/08/2019 16:01
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